Comparative study of emotional facial expression recognition among Prader-Willi syndrome subtypes.

BACKGROUND: Prader-Willi syndrome (PWS) is a congenital disease caused by a rare and generally non-inherited genetic disorder. The inability to recognise facial expressions of emotion is an apparent social cognition deficit in people diagnosed with PWS. The main objective of the present study is to compare the ability to recognise emotional facial expression, in both non-contextualised and contextualised scenarios, among the main subtypes of PWS and a control group. METHODS: The sample consisted of 46 children divided into three groups: deletion (n = 10), maternal uniparental disomy (mUPD) (n = 13) and control (n = 23). The protocol included the Facially Expressed Emotion Labeling and the Deusto-e-Motion 1.0. RESULTS: The control group recognised facial emotions more accurately and quickly in both non-contextualised and contextualised scenarios than children with PWS, regardless of genetic subtype. Despite no differences being detected between PWS subtypes when non-contextualised scenarios were analysed, in contextualised situations, a longer reaction time was observed in children with the mUPD subtype. CONCLUSIONS: This is the first study to assess the ability to recognise emotional facial expressions in contextualised situations among PWS subtypes and a control group. The findings suggest that some of the social cognitive deficits evidenced in children with mUPD PWS may be similar to those in autism spectrum disorder.

Experimental and numerical investigation of waterjet interaction with liver in connection with surgical technique.

Hepatectomy, or liver resection, is a process by which through surgery part or all of the liver is removed. In this operation, less bleeding, negligible damage and fast removal are the most important requirements. Surgery through waterjet is one of the most efficient techniques which is widely used in hepatectomy. Some clinical studies are conducted to investigate waterjet method in liver resection. In the present study interaction of waterjet with liver during the process of the surgery is investigated in terms of mechanical engineering. For this purpose, a system of waterjet is designed to consider the interaction of waterjet with liver at different nozzle diameter and velocities. For validation, SPH-FEM model is used to analyze waterjet interaction with hyperelastic liver. In this model, liver cutting is simulated using element deletion defined by a subroutine code based on maximum principal strain criterion. Depth of cut along with degraded volume are measured experimentally and compared with simulated method. Results show that good agreement exists between experimental and simulation finding. By comparing depth of cut in the experimental and simulation results, it can be seen that liver behavior changes from brittle to ductile by increasing waterjet velocity during the experimental tests. For the simulation, maximum principal strain threshold is set to be between 0.1 and 0.4. However, the best agreement between experimental and simulation results exists at maximum principal strain threshold equal to 0.2. The findings can help surgeons to find the best working range of waterjet device and the most efficient operation.

Characterization and function of promoters of silicon transporter genes PeLsi1-1 and PeLsi1-2 from moso bamboo (Phyllostachys edulis).

KEY MESSAGE: Promoters of moso bamboo silicon transporter genes PeLsi1-1 and PeLsi1-2 contain elements in response to hormone, silicon, and abiotic stresses, and can drive the expression of PeLsi1-1 and PeLsi1-2 in transgene Arabidopsis. Low silicon 1 (Lsi1) transporters from different species have been shown to play an important role in influxing silicon from soil. In previous study, we cloned PeLsi1-1 and PeLsi1-2 from Phyllostachys edulis and verified that PeLsi1-1 and PeLsi1-2 have silicon uptake ability. Furthermore, in this study, the promoters of PeLsi1-1(1910 bp) and PeLsi1-2(1922 bp) were cloned. Deletion analysis identified the key regions of the PeLsi1-1 and PeLsi1-2 promoters in response to hormone, silicon, and abiotic stresses. RT-qPCR analysis indicated that PeLsi1-1 and PeLsi1-2 were regulated by hormones, salt stress and osmotic stress. In addition, we found that the driving activity of the PeLsi1-1 and PeLsi1-2 promoters was regulated by 2 mM K2SiO3 and PeLsi1-1-P3 ~ P4 and PeLsi1-2-P4 ~ 5 were the regions regulated by silicon. Overexpression of PeLsi1-1 or PeLsi1-2 driven by 35S promoter in Arabidopsis resulted in a threefold increase of Si accumulation, whereas transgenic plants showed deleterious symptoms and dwarf seedlings and shorter roots under 2 mM Si treatment. When the 35S promoter was replaced by PeLsi1-1 or PeLsi1-2 promoter, a similar Si absorption was achieved and the transgene plants grew normally. This study, therefore, demonstrates that the promoters of PeLsi1-1 and PeLsi1-2 are indeed effective in driving the expression of moso bamboo Lsi1 genes and leading to silicon uptake.

Incessant Ventricular Tachycardia: An Atypical Presentation of Chronic Eosinophilic Leukemia.

Hypereosinophilic syndrome comprises a diverse and intricate array of rare disorders, exhibiting clinical manifestations that extend across various medical subspecialties. Within its myeloid form, chronic eosinophilic leukemia represents a rare myeloid malignancy characterized by severe hematological complications and distinctive organ dysfunction, notably affecting the cardiovascular system. This report presents a rare case of chronic eosinophilic leukemia and Loeffler syndrome with an initial presentation of ventricular tachycardia.

Are 19del and L858R really different disease entities?

Clinicians have recognized the similarities and differences between the two subtypes of common epidermal growth factor receptor (EGFR) mutations, but actual treatment strategies have not yet changed. The L858R mutation can be understood by considering the pharmacological conformational plasticity of the receptor protein and the presence of other co-occurring mutations, whether subtypes of EGFR or non-EGFR mutations and differences in downstream signaling pathways. As long as we know that molecular differences lead to biological differences, it is a challenge for all of us that our treatment strategies must change.

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Detection Of CCR5 Delta-32 Mutation Using High-Resolution Melting Curve Analysis: Challenges and Facts.

INTRODUCTION: The C-C chemokine receptor type 5 (CCR5) is a major co-receptor for human immunodeficiency virus (HIV). Some individuals carry the CCR5 delta-32 genetic polymorphism. People with homozygous CCR5 delta-32 gene are nearly completely resistant to HIV-1 infection. High-resolution melting curve (HRM) analysis is a post-PCR technique utilized for identifying genetic variations in a quick, affordable, and closed-tube assay. The objective of this study was to develop an HRM assay for easy detection of delta-32 mutations. MATERIALS AND METHODS: DNA was extracted from peripheral blood mononuclear cells. HRM was performed to detect delta-32 mutation. The study investigated the impact of various factors, including annealing temperature, template concentration, touchdown PCR, additives, amplicon size, and program settings, on HRM Tm differentiation. RESULTS: It was expected that there would be a 4°C Tm difference between amplicons with and without delta-32 mutation, but the test showed a difference of only 2.3°C. In attempts to identify heterozygote delta-32 variants, a Tm difference of only 0.4°C could be achieved. Various modifications were applied, such as adjusting the template concentration, using touchdown PCR, and adding DMSO and glycerol. However, none of these changes helped to differentiate the Tm effectively, especially in delta-32 heterozygote samples. CONCLUSION: The HRM test identified four samples with heterozygote mutations in each HIV-infected (8.89%) and control (5.72%) groups. More importantly, this study showed that identifying the delta-32 mutation of the CCR5 gene using HRM assay is not as straightforward as previously suggested in some literature, and it requires special setup conditions.

De novo and inherited micro-CNV at 16p13.11 in 21 Chinese patients with defective cardiac left-right patterning.

Objective: Copy number changes at Chromosomal 16p13.11 have been implicated in a variety of human diseases including congenital cardiac abnormalities. The clinical correlation of copy number variants (CNVs) in this region with developmental abnormalities remains controversial as most of the patients inherit the duplication from an unaffected parent. Methods: We performed CNV analysis on 164 patients with defective left-right (LR) patterning based on whole genome-exome sequencing (WG-ES) followed by multiplex ligation-dependent probe amplification (MLPA) validation. Most cases were accompanied with complex congenital heart disease (CHD). Results: CNVs at 16p13.11 were identified in a total of 21 cases, accounting for 12.80% (21/164) evaluated cases. We observed a marked overrepresentation of chromosome 16p13.11 duplications in cases when compared with healthy controls according to literature reports (15/164, 9.14% versus 0.09% in controls). Notably, in two independent family trios, de novo 16p13.11 micro-duplications were identified in two patients with laterality defects and CHD. Moreover, 16p13.11 micro-duplication was segregated with the disease in a family trio containing 2 affected individuals. Notably, five coding genes, NOMO1, PKD1P3, NPIPA1, PDXDC1, and NTAN1, were potentially affected by micro-CNV at 16p13.11 in these patients. Conclusion: Our study provides new family-trio based evidences to support 16p13.11 micro-duplications predispose individuals to defective cardiac left-right patterning and laterality disorder.

European Society of Immunodeficiencies guidelines for the management of patients with congenital athymia.

Congenital athymia is a life-limiting disorder due to rare inborn errors of immunity causing impaired thymus organogenesis or abnormal thymic stromal cell development and function. Athymic infants have a T-B+NK+ immunophenotype with profound T lymphocyte deficiency and are susceptible to severe infections and autoimmunity. Patients variably display syndromic features. Expanding access to newborn screening for severe combined immunodeficiency (SCID) and T lymphocytopaenia and broad genetic testing, including next-generation sequencing technologies, increasingly facilitate their timely identification. The recommended first-line treatment is allogeneic thymus transplantation, which is a specialized procedure available in Europe and the United States. Outcomes for athymic patients are best with early diagnosis and thymus transplantation before the development of infectious and inflammatory complications. These guidelines on behalf of the European Society of Immunodeficiencies provide a comprehensive review for clinicians who manage patients with inborn thymic stromal cell defects, and offer clinical practice recommendations focused on the diagnosis, investigation, risk stratification and management of congenital athymia, with the aim of improving patient outcomes.

Hearing Loss in Children with 22q11.2 Deletion Syndrome.

OBJECTIVES: Hearing loss is considered common in children with 22q11.2 deletion syndrome (22q11.2DS), with a few prior studies reporting a 32%-78% prevalence; mild-moderate conductive hearing loss has been reported most commonly. Overall, however, there remains a paucity of data regarding the frequency, type, age, and progression of hearing loss in children with 22q11.2DS. METHODS: Retrospective chart review was completed, and data combined for two large 22q centers. Inclusion criteria were children with 22q11.2DS and a documented audiogram. Data extracted included a laboratory-confirmed chromosome 22q11.2 deletion; co-morbidities; results of all audiograms and radiologic temporal bone imaging; and otologic surgical procedures. RESULTS: One thousand seven hundred sixty-nine charts were reviewed; 775 met inclusion criteria. Of these, 563 (73%) children had at least one abnormal audiogram demonstrating hearing loss. A total of 2,536 audiograms were reviewed; 74% of these showed abnormal hearing in at least one ear. Most of the hearing loss was conductive (right ear 76%; left ear 69%) and mild severity. For the children with SNHL, 90% of all follow-up audiograms were stable without progression. Hearing loss was identified across all pediatric age ranges. Ear tube placement occurred in 39% of children. CONCLUSION: This study confirms the high incidence of hearing loss for children with 22q11.2DS at some point in their childhood. In our cohort, hearing loss occurred in 73% of children and was most often conductive and mild in severity. The results highlight the importance of otolaryngology and audiology involvement in managing children with 22q11.2DS for timely diagnosis and treatment of hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Screening of the Combined Risk of Genetics and Epidemiology on Infertility Among Indian Men: Synergistic Effect of AZFc Partial Deletions and Habits of Smokeless Chewing Tobacco.

The AZFc partial deletions of Y chromosome and lifestyle/epidemiological factors such as the use of smokeless chewing tobacco (SCT) exhibit intriguing variations in their association with male infertility across the population, ethnicity, and genetic background. Here, a pioneering attempt has been made to elucidate the interactions of such deletions with the habits of SCT consumption among the participating individuals, using their large epidemiological data. This screening program was conducted among Bengali-speaking men in West Bengal, India. We screened the prevalence and association of distinct partial deletions (gr/gr, b1/b3, and b2/b3) of the AZFc region using locus-specific sequence-tagged site (STS) markers among 728 case subjects and compared them with 264 ethnicity- and age-matched proven-fertile control men. The recorded epidemiological data of the study group and the outcome of partial deletion analysis were compiled to frame the plausible Gene × Epidemiological factor (G × E) interactions. The gr/gr deletion was reported to be significantly associated with azoospermic (p = .0015, odds ratio [OR] = 3.413) and oligozoospermic (p = .0382, OR = 3.012) case subgroups, and b1/b3 deletions were also detected among the infertile persons only. The G × E model revealed that men who carried microdeletions as well as were SCT users had an elevated risk of infertility (p = .002, OR = 6.38). The study highlights the fact that AZFc partial deletions and SCT, when co-occurred, synergistically increase the risk of infertility among men. This work helps to get more insight into the etiology of male infertility in the light of gene-environmental interaction.

An Assessment of Adverse Events in Patients with 22q11.2 Deletion Syndrome Undergoing Palatoplasty: An Analysis of the NSQIP Pediatric Database.

BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) Pediatric database has been used to identify factors related to adverse surgical outcomes in pediatric and craniofacial surgical procedures. Focusing on a historically "higher-risk" population, our aim was to assess the impact of demographics, comorbidities, and 22q11.2 deletion syndrome (22QDS) diagnosis on 30-day postoperative complications in patients undergoing primary palatoplasty. METHODS: We used the 2012-2020 NSQIP Pediatric database to identify patients ≤3 years with and without 22q11.2 deletion syndrome who underwent primary palatoplasty. Demographics, comorbidities, and perioperative characteristics were compared between those with and without 22QDS. Logistic regression was used to determine if children with 22QDS were more likely to experience a 30-day postoperative complication or readmission. RESULTS: There were 10,745 patients ≤3 years old who underwent primary palatoplasty; 83 (0.8%) of whom had 22QDS and 10,662 (99.8%) did not. Children with 22QDS were older when they underwent primary palatoplasty and more likely to have comorbidities. A total of 513 patients (4.8%) experienced a postoperative complication within 30 days and 255 were readmitted (2.4%). Of the 513, 8 (9.6%) had a 22QDS diagnosis and 505 (4.7%) did not. A diagnosis of 22QDS was not a significant independent risk factor for a complication (adjusted odds ratio (aOR) = 1.13; 95% confidence interval (CI): 0.50-2.54) or readmission (aOR = 1.74; 95% CI: 0.74-4.13) within 30 days. CONCLUSION: This study found that the diagnosis of 22QDS was not an independent predictor of post-palatoplasty complication risk, and in fact 30-day complications are rare for those patients undergoing cleft palate repair, even among those patients with 22QDS.

Concurrent HBsAg and anti-HBs induced by a preS deletion mutant in a chronic hepatitis B patient.

This study analyzed the origins of concurrent hepatitis B surface antigen (HBsAg) and HBsAg antibodies (anti-HBs) in a patient with chronic hepatitis B virus (HBV) infection. The levels of serological markers of HBV infection were determined by enzyme-linked immunosorbent assay (ELISA). The preS/S gene was analyzed by gene amplification and sequencing. The tests revealed that HBsAg and anti-HBs coexisted in this patient with mixed infections of the full-length preS/S virus strain and preS1 183 bp deletion mutant, and both the mutant and the anti-HBs were no longer present after one year, which means that the mutant strain was cleared by the detected antibodies. Thus, it is speculated that anti-HBs antibodies targeted specifically to the preS1 deletion mutant strain instead of the strain with the full-length large S protein were produced. This mechanism is quite different from other immunopathogenic mechanisms for concurrent HBsAg and anti-HBs.

Predictive machine learning models based on VASARI features for WHO grading, isocitrate dehydrogenase mutation, and 1p19q co-deletion status: a multicenter study.

The objective of our study was to develop predictive models using Visually Accessible Rembrandt Images (VASARI) magnetic resonance imaging (MRI) features combined with machine learning techniques to predict the World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation status, and 1p19q co-deletion status of high-grade gliomas. To achieve this, we retrospectively included 485 patients with high-grade glioma from the First Affiliated Hospital of Xinjiang Medical University, of which 312 patients were randomly divided into a training set (n=218) and a test set (n=94) in a 7:3 ratio. Twenty-five VASARI MRI features were selected from an initial set of 30, and three machine learning models - Multilayer Perceptron (MP), Bernoulli Naive Bayes (BNB), and Logistic Regression (LR) - were trained using the training set. The most informative features were identified using recursive feature elimination. Model performance was assessed using the test set and an independent validation set of 173 patients from Beijing Tiantan Hospital. The results indicated that the MP model exhibited the highest predictive accuracy on the training set, achieving an area under the curve (AUC) close to 1, indicating perfect discrimination. However, its performance decreased in the test and validation sets; particularly for predicting the 1p19q co-deletion status, the AUC was only 0.703, suggesting potential overfitting. On the other hand, the BNB model demonstrated robust generalization on the test and validation sets, with AUC values of 0.8292 and 0.8106, respectively, for predicting IDH mutation status and 1p19q co-deletion status, indicating high accuracy, sensitivity, and specificity. The LR model also showed good performance with AUCs of 0.7845 and 0.8674 on the test and validation sets, respectively, for predicting IDH mutation status, although it was slightly inferior to the BNB model for the 1p19q co-deletion status. In conclusion, integrating VASARI MRI features with machine learning techniques shows promise for the non-invasive prediction of glioma molecular markers, which could guide treatment strategies and improve prognosis in glioma patients. Nonetheless, further model optimization and validation are necessary to enhance its clinical utility.

An Auto-Reading probe system for detecting deletion mutations In liquid biopsy with direct quantification of mutation abundance.

Background: Deletion mutations have been confirmed to be closely related to the occurrence and progression of different hereditary diseases and tumors. Specifically, the deletion of a small number of bases is more challenging to be captured and differentiated. In non-invasive prenatal testing (NIPT) and liquid biopsy targeting circulating tumor DNA, obtaining accurate mutation abundance in targeted DNA is a crucial step in the detection process. However, the quantification of mutation abundance with existing methods is not accurate enough. Results: Herein, we developed the " Auto-Reading" probe detection system based on our previous work. Through theoretical modeling and experimental calculations, we verified the successful application of our system in NIPT and early cancer diagnosis, enabling effective discrimination of different mutant abundances. Significance: Our method overcomes the interference of reaction concentrations on signal detection, allowing direct quantification of mutation abundance without the need for purification of PCR products. The detection system is cost-effective and feasible for laboratory use. We believe the system will facilitate broad applications in mutation detection.

HNF1ß, LHX1, and GGNBP2 deletion contributed to kidney and reproductive dysfunction in 17q12 deletion syndrome: evidence from a case report.

17q12 deletion syndrome is a chromosomal abnormality, where there is a small missing piece (deletion) of genetic material on the long arm (q) of chromosome 17. Sign and symptoms can vary widely among different patients. Recently, a patient was diagnosed with 17q12 deletion syndrome in our hospital, and the clinical characteristics presented as absence of the right kidney, compensatory hypertrophy of the left kidney, multiple small cysts in the left kidney, pancreatic atrophy, hypomagnesemia, bowed uterus, multiple follicular cysts in both lobes of the thyroid gland, and maturity-onset diabetes of the young type 5 (MODY-5). A 1.5-Mb deletion with haploinsufficiency for 20 genes within the 17q12 region was found through copy number variation (CNV) analysis based on metagenomic next-generation sequencing (mNGS) technology. In addition to HNF1B absence, the LIM-class homeobox 1 transcription factor (LHX1) and GGNBP2 absence was also involved in regulation of kidney development and the reproductive system through bioinformatics analysis. The inheriting risk of 17q12 deletion syndrome is about 50%, and it is recommended to provide genetic counseling to all patients who are suspected or diagnosed with the syndrome.

Prenatal diagnosis of monozygotic twins with phenotypic differences in chromosome 17q12 deletion syndrome.

We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non-genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome.

Genetic Manipulation of Candida glabrata.

Candida glabrata (Nakaseomyces glabratus) is an opportunistic fungal pathogen that has become a significant concern in clinical settings due to its increasing resistance to antifungal treatments. Understanding the genetic basis of its pathogenicity and resistance mechanisms is crucial for developing new therapeutic strategies. One powerful method of studying gene function is through targeted gene deletion. This paper outlines a comprehensive protocol for the deletion of genes in C. glabrata, encompassing primer design, preparation of electrocompetent cells, transformation, and finally confirmation of the gene deletion. The protocol begins with the identification and design of primers necessary for generating deletion constructs, involving the precise targeting of up- and downstream regions flanking the gene of interest to ensure high specificity and efficiency of homologous recombination. Followed is the preparation of electrocompetent cells, a critical step for successful transformation. Transformation of the competent cells is achieved through electroporation, facilitating the introduction of exogenous DNA into the cells. This is followed by the selection and confirmation of successfully transformed colonies. Confirmation involves the use of colony PCR to verify the correct integration of the NAT resistance cassette and deletion of the target gene. © 2024 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Primer design for gene deletion in C. glabrata Basic Protocol 2: Preparing competent C. glabrata cells Basic Protocol 3: Transforming C. glabrata using electroporation Basic Protocol 4: Confirming deletion strains with colony PCR.

Platelet changes and bleeding symptoms in children, adolescents, and adults with 22q11.2 deletion syndrome.

BACKGROUND: The deletion region of 22q11.2 deletion syndrome (22q11.2DS) contains a gene encoding glycoprotein Ibß (GPIbß), which is required to express the GPIb/IX/V complex on the platelet surface. Therefore, patients with 22q11.2DS may have congenital platelet disorders. However, information is limited on platelets and bleeding symptoms. In this study, we investigated clinical information, including bleeding symptoms, platelet counts, and GPIb expression levels in children and adolescents/adults with 22q11.2DS. PROCEDURE: Thirty-two patients with 22q11.2DS were enrolled in a prospective cohort study between 2022 and 2023 at outpatient clinics within our institute. RESULTS: The median platelet counts in adolescents/adults with 22q11.2DS were significantly lower than those in children (p < .0001). A gradual decrease was found along with increasing age (p = .0006). Values of median GPIb expression on platelet surfaces (66% in children and 70% in adolescents/adults) were significantly lower than those in healthy controls (p < .0001 and p = .0002). Bleeding symptoms included surgery-related bleeding (52%), purpura (31%), and epistaxis (22%); most of them were minor. The median International Society on Thrombosis and Hemostasis bleeding assessment tool score was not significantly different between children and adolescents/adults (p = .2311). CONCLUSION: Although there was an age-related decrease in platelet count and a disease-related decrease in GPIb expression, no difference in bleeding symptoms was found between children and adolescents/adults. 22q11.2DS overall had minor bleeding symptoms in daily life, and the disease had little effect on spontaneous bleeding. However, some patients had major bleeding events; further accumulation of data on hemostasis during surgery and trauma is required.

InDel mutations within the bovine PER2 gene are significantly associated with reproductive traits.

Functioning as a key regulator of circadian rhythms, the PER2 gene exerts a substantial impact on the reproductive traits of animals. However, the effect of the PER2 gene on ovarian development remains unclear. In order to examine the relationship between bovine reproductive trait and the PER2 gene, a total of 901 ovarian samples were collected, categorized into different oestrus cycles (proestrus, oestrus, post-oestrus, anoestrous), and subjected to analysis for two potential insertion/deletions (InDels) in the PER2 gene. Through agarose gel electrophoresis and DNA sequencing, two polymorphic deletion mutations (P2-D5-bp, P3-D13-bp) were identified. Furthermore, a significant association between mature follicle diameter and P2-D5-bp was found (P < 0.05). Additionally, several significant correlations with ovarian length, width, height, and white body diameter were found for P3-D13-bp (P < 0.05). These findings suggested that the bovine PER2 gene plays an important role in above-mentioned reproductive traits, offering new avenues for improving cow fertility through marker-assisted selection (MAS).